Microtubule stabilization promoted axonal regeneration and functional recovery after spinal root avulsion

Abstract

A spinal root avulsion injury disconnects spinal roots with the spinal cord. The rampant motoneuron death, inhibitory CNS/PNS transitional zone (TZ) for axonal regrowth and limited regeneration speed together lead to motor dysfunction. Microtubules rearrange to assemble a new growth cone and disorganized microtubules underline regeneration failure. It has been shown that microtubule-stabilizing drug, Epothilone B, enhanced axonal regeneration and attenuated fibrotic scaring after spinal cord injury. Here, we are reporting that after spinal root avulsion+ re-implantation in adult rats, EpoB treatment improved motor functional recovery and potentiated electrical responses of motor units. It facilitated axons to cross the TZ and promoted more and bigger axons in the peripheral nerve. Neuromuscular junctions were reformed with better preserved postsynaptic structure, and muscle atrophy was prevented by EpoB administration. Our study showed that EpoB was a promising therapy for promoting axonal regeneration after peripheral nerve injury.

Keywords: Epothilone B; intrinsic regrowth capability; motoneurons; peripheral nerve regeneration.